Current and future pharmacological therapies for managing cirrhosis and its complications

Abstract

Due to the restrictions of liver transplantation, complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis. This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications, together with discussion of current controversies and potential future directions. PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety, efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis. Non-selective beta-blockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices, but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation. Recent observational studies suggest protective, haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation. The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy; recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis. Diuretics remain the mainstay of uncomplicated ascites treatment, and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites. Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications. Despite initial hepatotoxicity concerns, safety of statin administration has been demonstrated in compensated cirrhosis. Furthermore, statins are suggested to have protective effects upon fibrosis progression, decompensation and mortality. Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting. Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis, and may impede hepatic fibrogenesis and decompensation. Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management, nutritional optimisation and patient education.

The bacterial spectrum of spontaneous bacterial peritonitis in patients with cirrhosis of liver.

“…3 Factors responsible for poor prognosis of SBP in cirrhosis that are reported in different studies are age, child score, intensive care admission, nosocomial origin, hepatic encephalopathy, high serum values of creatinine and bilirubin, culture positivity, bacterimia and CARD15/NOD2 variants were identified as risk factor on genetic level. 4 The Bacterial Translocation (BT) is known as the most common cause of SBP. 5 BT on a limited scale to mesenteric lymph nodes (MLN) is considered physiological, but more severe BT is considered pathological.…”

“…These are the most common organism causing SBP and studies on DNA sequencing revealed the identity of bacteria genotypically in MLN and ascites. 5,6 Three factors are identified in causing BT in cirrhosis of liver; 4 • Alteration in microbiota of the gut.…”

“…5 In cirrhosis of liver increased number of colonies in gut and changes in their composition is secondary to decrease in paneth cell defenses, reduced motility of the intestine as well as reduced secretions from pancreatobiliry system and portal hypertension enteropathy. 4 The most common causative organisms for SBP are aerobic Gram-negative bacteria belonging to the family of Enterobacteriaceae and nonenterococcal Streptococcus species. However sever infection with gram positive infections are emerging.…”

Pharmacological management of portal hypertension: current status and future

“…[ 3 ] The pharmacological management of PHT aims to reduce PP and prevent PHT-related complications. [ 4 , 5 ] Given that PP is determined by portal blood flow and hepatic vascular resistance, [ 4 ] currently used drugs are mainly targeted to modulate the increased liver blood flow, such as reducing hyperdynamic circulation, renin-angiotensin-aldosterone system activation, vascular hyperplasia, and collateral circulation formation, or decrease intravascular resistance, such as inhibiting liver fibrosis, regenerative nodules, and angiogenesis. [ 6 ] In the setting of PHT, arterial vasodilation occurs both in the splanchnic and systemic circulation, therefore, activates the neurohumoral and vasoconstrictive systems, which leads to sodium and water retention, increased blood volume, and increased cardiac output.…”

Ефективність Застосування Аторвастатину При Поєднанні Алкогольної Хвороби Печінки Та Артеріальної Гіпертензії

“…Численні дослідження показали, що, окрім впливу на сироватковий рівень ліпідів, статинам властиві плейотропні ефекти, які зумовлюють їх застосування не тільки при хворобах серця і судин, а й за гострих уражень нирок, нефропатії, панкреатиту, хронічного обструктивного захворювання легень, венозної тромбоемболії, деменції, когнітивної та еректильної дисфункцій, онкопатології, системного червоного вовчака, тяжкого сепсису та при інших захворюваннях [1][2][3]. Останнім часом зросла кількість повідомлень щодо перспективності їх використання при захворюваннях печінки [4][5][6]. Відомо також про різноманітні побічні ефекти статинів (виникнення міозитів, рабдоміолізу, катаракти, збільшення ризику розвитку цукрового діабету, дозозалежне зростання активності печінкових ферментів тощо).…”